Session 3 - part 1

Enzo Medico^1,2,3

¹ EurOPDX Research Infrastructure (EDIReX) project coordinator

² University of Torino, Italy

³ Candiolo Cancer Institute, FPO- IRCCS, Italy

Patient-derived cancer xenografts (PDXs) are increasingly recognised as useful models to evaluate in vivo treatment efficacy and discover sensitivity and resistance biomarkers with immediate clinical relevance.

To effectively recapitulate and therapeutically interrogate the heterogeneity of human cancer, thirteen European research centres and university hospitals joined forces in 2013 to start EurOPDX, an academic research consortium that now gathers 18 institutions throughout Europe and in the US (europdx.eu).

The goal of the Consortium is to maximize exploitation of PDXs and other patient-derived models for cancer research by:

1. integrating institutional collections into a multicentre repository now reaching more than 1500 models for 30+ different cancer types
2. defining common standards to improve the quality and reproducibility of oncology preclinical data
3. sharing models within and outside the Consortium to perform collaborative precision oncology “xenopatient” trials
4. developing and testing more advanced patient-derived cancer models, both in vivo and in vitro, to more closely and effectively recapitulate tumour biology and response to therapy

Building on its first successes, EurOPDX has now teamed up with other key academic and SME partners in a four-year project to build the “EurOPDX Distributed Infrastructure for Research on patient-derived Xenografts" (EDIReX, funded under the EU’s H2020 research and innovation programme, grant no. 731105) (europdx.eu/europdx-research-infrastructure).

This new cutting-edge European infrastructure will offer access to PDX resources for academic and industrial cancer researchers through six state-of-the-art installations or “nodes”, which we will present together with the specific objectives of the project. Access to the resource, including the distribution of cryopreserved samples from established models, the structured biobanking of user-developed models and the performance of drug efficacy studies, will be offered through a grant application system termed “Trans-national Access (TA)” to open on the 31st October 2018. Selection of models by users will be facilitated by the newly-developed EurOPDX Data Portal, of which a prototype will be presented.

A demo version of the EurOPDX data portal will be available for testing during Poster session 2 (October 2nd from 21:00).

Through the EurOPDX research infrastructure, we aim to improve preclinical and translational cancer research and promote innovation in oncology by integrating a European PDX repository and facilitating access to this much-needed resource for European and worldwide researchers.

Nathalie Conte¹, Jeremy Mason¹, Csaba Halmagyi¹, Abayomi Mosaku¹, Steven B Neuhauser², Dale A Begley², Debra M Krupke², Helen Parkinson¹, Terrence Meehan¹, Carol J Bult²

¹ EMBL-EBI, Hinxton, Cambridge, UK

² The Jackson Laboratory, Bar Harbor, USA

Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, drug response and for tailoring chemotherapeutic approaches to individual patients. PDX models are produced and made available in repositories managed by small academic labs, large research consortia and contract research organizations. Because of the distributed and heterogeneous nature of PDX repositories, finding relevant models of interest to investigators is a challenge.

To address this issue, The Jackson Laboratory and EMBL-EBI have co-developed the PDX Finder*, a comprehensive open global catalogue of PDX models and their associated data across resources. In support this initiative, we coordinated the community initiative to develop the PDX models Minimal Information standard (PDX-MI) that defines the minimal information necessary for describing key elements of a PDX model including the clinical attributes of a patient’s tumor, methods of implantation, host strain, and quality assurance methods used for model validation**. PDX-MI serves as the basis for PDX Finder’s comprehensive search and attribute filtering options (e.g., tumor histology, molecular variant, drug response).

Within PDX Finder, model attributes are harmonized and integrated into a cohesive ontological data model that supports consistent searching across the originating resources. From PDX Finder, direct links to these resources are provided to allow users to contact the relevant institution for model acquisition and further collaboration. PDX Finder is formally collaborating with several worldwide consortia including PDXnet and EurOPDX to increase “findability” of PDX models and to advance cancer research and drug discovery. PDX Finder is currently displaying over 1900 PDX models for a wide variety of cancers and is actively recruiting more models.

The community is invited to explore and provide feedback on our portal as we build this rich resource at www.pdxfinder.org